Kasarpalkar Nikhil J, Kothari Sweta T, Dave Usha P
Department of Biochemistry;
Department of Virology;
Ann Neurosci. 2014 Oct;21(4):129-33. doi: 10.5214/ans.0972.7531.210403.
Autism Spectrum Disorder (ASD) is a complex neurobehavioral syndrome with no known biomarker so far for early detection. It has been challenging, both to classify typical autism and associate a suitable biomarker with clinical phenotype spectrum. Brain-derived neurotrophic factor (BDNF) has emerged as a key neurotrophin regulating synaptic plasticity, neuronal differentiation and survival.
Recently, BDNF depletion is reported in neurodegenerative as well as in psychiatric disorders, associated with severity of neurological dysfunction. Role of BDNF as a biomarker in ASD is gaining significance. Pre-clinical results have linked BDNF depletion in autism and mental retardation, however, with conflicting findings.
In view of this, a preliminary study was carried out to measure serum BDNF levels in 48 children with ASD and mental retardation, and 29 age-matched controls.
Serum BDNF levels were found significantly higher (p<0.001) in atypical autistic subjects (clinically milder phenotype) as compared to controls, but not in typical ASD cases (clinically severe phenotype). BDNF levels were significantly lower in females with typical/Rett Syndrome (p<0.05), but not in males with typical autism (p>0.1), as compared to controls. Lower BDNF levels indicate impairment in neuroprotective mechanism, while higher levels may imply a manifested protective response.
Our study highlights the differential BDNF response based on the severity of neurobehavioral deficit, indicating a possible neuroprotective role of this molecule and supporting its exploration in targeted therapy in ASD.
自闭症谱系障碍(ASD)是一种复杂的神经行为综合征,目前尚无用于早期检测的已知生物标志物。对典型自闭症进行分类并将合适的生物标志物与临床表型谱相关联一直具有挑战性。脑源性神经营养因子(BDNF)已成为调节突触可塑性、神经元分化和存活的关键神经营养因子。
最近,据报道在神经退行性疾病以及精神疾病中存在BDNF耗竭,这与神经功能障碍的严重程度相关。BDNF作为ASD生物标志物的作用正变得越来越重要。临床前研究结果已将自闭症和智力迟钝中的BDNF耗竭联系起来,然而,结果相互矛盾。
鉴于此,开展了一项初步研究,以测量48名患有ASD和智力迟钝的儿童以及29名年龄匹配的对照组儿童的血清BDNF水平。
与对照组相比,非典型自闭症患者(临床症状较轻的表型)的血清BDNF水平显著更高(p<0.001),但典型ASD病例(临床症状严重的表型)并非如此。与对照组相比,患有典型自闭症/雷特综合征的女性BDNF水平显著更低(p<0.05),但患有典型自闭症的男性则不然(p>0.1)。较低的BDNF水平表明神经保护机制受损,而较高的水平可能意味着明显的保护反应。
我们的研究强调了基于神经行为缺陷严重程度的BDNF差异反应,表明该分子可能具有神经保护作用,并支持在ASD的靶向治疗中对其进行探索。